It has been established that early-onset Alzheimer’s disease can be caused by a change in a number of genes — the gene of the amyloid precursor protein located in chromosome 21 (A. Goate et al., 1991), the presenilin 1 gene localized on chromosome 14 (E Rogaev et al., 1995; R. Sherrington et al., 1995) and presenilin 2 gene, located on chromosome 1 (E. Levy-Lahad et al., 1995). Allele 4 of the apolipoprotein-E gene (APO-E4), localized on chromosome 19, a risk factor for late-onset asthma (A. Saunders et al., 1993).
Various mutations associated with the development of AD ultimately cause an accumulation of beta-amyloid protein ( A) in the brain , consisting of 39-43 amino acids and an essential component of senile plaques. Mutations increase the production of A or lead to the formation of A with two additional amino acid residues. Lengthening A triggers the accelerated aggregation of this protein. A is a neurotoxin that causes neurodegenerative changes, and its neurotoxic effect can be accompanied by epileptic activity (F. LaFerla, 1995; G. Cole, S. Frautschy, 1996). In clinically healthy relatives of patients with asthma many years before the development of the disease in the blood, an increase in the level of обнаруженоA was found (NR Graff-Radford et al., 1998). It is assumed that clinical symptoms manifest when A begins to be deposited in the brain. A significantly enhances the neurotoxic effect of the excitatory mediator glutamate (M. Mattson, 1990). As a result of excitotoxic, i.e. excitatory neurotoxic effects, long before the development of the disease in people genetically predisposed to asthma, the excitability of brain structures increases and their resistance to stress is significantly reduced, which is accompanied by stress disorders characteristic of stress. An increase in the excitability of brain structures in people genetically predisposed to asthma manifests itself in the form of an increase in the amplitude of the late components of visual evoked potentials, the appearance of acute forms bilateral synchronous high-amplitude theta and delta waves during hyperventilation, increased brain SCP (N.V. Ponomareva et al., 1998, 1999). It was also found that in relatives of patients with asthma during functional loads of cerebral blood flow increases significantly more than normal (SY Bookheimer, 2000). The consequence of increased sensitivity to stress is the previously described disorders of energy metabolism, chronic acidification of the brain, an increase in the intensity of free-radical processes, the accumulation of extracellular calcium, and eventually the death of neurons.
Cerebral acidosis affects the specific mechanisms of BA development. Experimental studies have shown that increased production of lactate in the brain disrupts the processing of the amyloid precursor protein and promotes the formation of beta-amyloid protein deposits (GJ Brewer, 1997; GJ Bosman et al., 1997).